When a wound is formed on a tissue of an organism, such as a skin, a muscle and an organ, by an operation, an accident or other causes, expeditiously stopping bleeding from the wound is one of the most critical matters from the viewpoint of the success of the operation and the sustenance of the healing power (activity) of the organism.
Hitherto, any rupture or wound formed on a soft tissue, such as a skin, a muscle, an organ and a blood vessel, has generally been kept sutured until it is completely healed.
However, not only must sutures be sterilized prior to use, but also suturing with firm knots requires skill.
In addition to the suturing, physical methods for stopping bleeding from wounded part are known, which include electrical, infrared and laser ray coagulations.
In these methods as well, there are problems that hemostasis requires skill, and that special instruments and devices are requisite. In particular, these methods have been unavailable for a first aid for slight skin wounds, etc.
Apart from the physical methods, another hemostasis is known in which a local hemostatic agent is applied to bleeding part. With respect to such a local hemostatic agent, attention is being drawn to an adhesive as a material capable of easily joining the edges of a wound (rupture).
Various adhesives for soft tissue are now known, which include a cyanoacrylate adhesive composed of an acrylic ester having a cyano group at its .alpha.-position and a fibrin paste obtained by mixing fibrinogen with thrombin.
The cyanoacrylate adhesive is characterized by requiring no sterilization. However, it has drawbacks in that when the adhesive is present between tissues, the natural joining or natural healing of the tissues is blocked, and that on the other hand, when a soluble substance is copresent so as not to block the union of the sections by the wound, the adhesion of the adhesive is decreased. Accordingly, a method is preferably adopted in which a piece of cloth of, for example, a polyester fiber having the adhesive applied thereto is pasted to a wounded part with contacting wound edges each other. Nevertheless, there has been a problem that the joining operation (inosculation) of the wound edges is not easy.
In case of applying an adhesive for joining cleaved blood vessels, there has been adopted a method in which first a support tube is inserted into each of the blood vessels, secondly the edges of the blood vessels are inosculated, thirdly three or four knotted stitches are put into the edges to fix the same, and finally the adhesive is applied to the inosculated part, or a method in which without the use of a support tube, the adhesive is applied to the part stitched and fixed. The use of the cyanoacrylate adhesive in these methods is accompanied by a problem that the blood flow must be stopped with a hemostat to stop bleeding, so that expeditious treatment cannot be performed.
The fibrin paste is produced by adding an aprotinin solution, thrombin, calcium chloride and other ingredients to human fibrinogen. The adhesive joins the edges of a wound by the blood coagulation action of the fibrinogen. However, the fibrin paste contains an ingredient obtained from a human (human fibrinogen) as indicated above, so that unfavorably, sterilization, especially treatment for inactivating various viruses, is inevitable. Further, there has been a problem that the adhesive strength is poor, so that in the event of an especially large wound, another fixing means, e.g., a suture, is required.
Moreover, the adhesive for use in the treatment of a wound (rupture) on a soft tissue of an organism not only must be nontoxic, but also should be able to join the edges of the wound irrespective of the presence of blood, body fluids, etc.
Therefore, there is a demand in the art for the development of an adhesive not only capable of expeditiously and easily joining the edges of a wound formed on a soft tissue of an organism by an operation or an accident irrespective of the presence of water attributed to blood, body fluids, etc. but also being nontoxic.
On the other hand, a traumatic or sticking adhesive plaster has been widely utilized for protecting a wounded part formed on an integument, such as skin and mucous membrane. A pressure sensitive skin adhesive has been used in such an adhesive plaster.
Various adhesives (pasting agents) may be used as the skin adhesive, which include acrylic adhesives such as a polymer obtained from an alkyl acrylate and acrylic acid (Japanese Patent Publication No. 31405/1977), a copolymer obtained from dodecyl methacrylate, (meth)acrylic acid and vinyl acetate (Japanese Laid Open Patent Publication No. 77167/1982), and a copolymer obtained from a (meth)acrylic ester having an intramolecular ether bond, acrylic acid and a (meth)acrylic ester (Japanese Laid Open Patent Publication No. 45412/1981). These acrylic pressure sensitive adhesives have advantageous properties that the tackiness to the skin is excellent, a good adherence is maintained for a prolonged period of time, contained drugs are not adversely deteriorated and the skin is not irritated, so that they are suitable for use as pressure sensitive adhesives.
Various types of the adhesive plasters each comprising a pressure sensitive adhesive base have been proposed and put into practical use. As such bases comprising pressure sensitive adhesives, those have been used which have tackiness and adherence over a broad range of temperatures, not exhibiting a tackiness decrease at low temperatures.
For example, for pasting to the skin, it is believed that a pressure sensitive adhesive base having desirable tackiness at about 30.degree. C. is satisfactory. Actually, however, pressure sensitive adhesive bases each having strong tackiness at 5.degree. to 10.degree. C. or lower temperatures have been proposed and put into practical use.
The reasons for the use of these pressure sensitive adhesive bases to date would be as follows:
(i) there has been a general concept that the broader the temperature range in which the pressure sensitive adhesive is available, especially at low temperatures, the greater the practical value thereof; and PA1 (ii) the greater the adhesion of the pressure sensitive adhesive to the skin at low temperatures, the higher the sticking performance thereof to the human skin and the less the peeling thereof by the flex of the skin. PA1 a (meth)acrylic ester containing an acid anhydride group represented by the above formula (I), or PA1 a mixture of a (meth)acrylic ester containing an acid anhydride group represented by the above formula (I) and a derivative of the (meth)acrylic ester represented by the above formula (Ia). PA1 the (meth)acrylate be methyl methacrylate, PA1 the poly(meth)acrylate be polymethyl methacrylate, and PA1 the polymerization initiator be tri-n-butylborane. PA1 the (meth)acrylate be present in an amount of 1 to 100 parts by weight, PA1 the poly(meth)acrylate be present in an amount of 0.1 to 100 parts by weight, and PA1 the polymerization initiator be present in an amount of 0.01 to 10 parts by weight.
However, the above acrylic pressure sensitive adhesives are poor in hydrophilicity (capability of absorbing water) and air permeability, so that they have the following drawbacks.
(1) When the medical pressure sensitive adhesive sheet having the conventional pressure sensitive adhesive layer provided therein is pasted to a wounded part for a long time, a swell occurs and the skin at the wounded part becomes hypersensitive to even a slight stimulus by a drug, etc., to cause contact dermatitis. Further, it is likely that an abnormal growth of various bacteria and fungi take place to induce secondary inflammation.
For example, a medical pressure sensitive adhesive sheet for inhibiting the above swell and contact dermatitis of the skin is disclosed in Japanese Patent Publication No. 4728/1964, which comprises a porous fibrous base material and, superimposed thereon through an open-cell layer, a pasting agent of a copolymer comprising an alkyl acrylate and acrylic acid. This sheet is excellent in air permeability, so that it does not cause swell.
However, the above pressure sensitive adhesive sheet has a drawback in that the base material and the pressure sensitive adhesive layer permits permeation of liquids, such as water, so that the protection of the wounded part is unsatisfactory.
Japanese Patent Publication No. 14108/1980 discloses a medical pressure sensitive adhesive sheet comprising a film which is excellent in steam permeability, such as a polyurethane film, and, superimposed thereon, a pressure sensitive adhesive layer composed of an acrylate copolymer or polyvinyl ethyl ether having a hydrophilic group in its molecule. This sheet exhibits a relatively good air permeability, and the permeability of the base film for a liquid, such as water, is less, so that the wounded part can be protected relatively well.
However, with respect to this pressure sensitive adhesive sheet, the hydrophilicity of the pressure sensitive adhesive is poor, so that the swell and contact dermatitis of the skin cannot be effectively prevented.
(2) The acrylic pressure sensitive adhesive has a drawback in that the adhesion thereof to the surface of an adherend in the wet or moist conditions, for example, sweating skin, is poor, and that, after application, peeling is likely to occur by perspiration of a large amount of sweat.
(3) The acrylic pressure sensitive adhesive has a drawback in that, once being applied to the surface of the skin, it is difficult to wash it away with water.
(4) The acrylic pressure sensitive adhesive has a drawback in that the solubility of a water-soluble drug, such as those in the form of a sodium, a potassium, an ammonium or a hydrochloric acid salt, therein is so low that it is difficult to prepare a medical pressure sensitive adhesive sheet comprising an acrylic pressure sensitive adhesive containing such a water-soluble drug.
In Japanese Laid Open Patent Publication No. 228868/1989, a copolymer is disclosed as one for overcoming the above drawbacks (1) to (4) of the acrylic pressure sensitive adhesive, which copolymer comprises a (meth)acrylic ester derivative and/or a (meth)acrylamide derivative having a saturated hydrocarbon residue containing a quaternary ammonium salt, and polyvinylpyrrolidone and/or diacetonacrylamide.
However, the water resistance of this copolymer is poor due to the inclusion of a large amount of the quaternary ammonium salt, so that the copolymer becomes excessively soft upon being exposed to sweating, and that it remains unremoved on the skin when being applied and stripped in the form of a sheet.
Japanese Laid Open Patent Publication No. 193057/1991 discloses a hydrophilic polymer comprising at least one member selected from glycosylethyl (meth)acrylate and glycosylpropyl (meth)acrylate as an essential ingredient, and also a medical adhesive comprising the above hydrophilic polymer and a plasticizer. The hydrophilic polymer and the medical adhesive purpose an increase of hydrophilicity. Further, Japanese Laid Open Patent Publication No. 146579/1991 discloses that a pressure sensitive adhesive comprising 20 to 80% by weight of an acrylate and/or a methacrylate having a straight chain alkyl group having at least 16 carbon atoms as an ester residue and 80 to 20% by weight of an acrylate and/or a methacrylate having an alkyl group having 2 to 8 carbon atoms on the average as an ester residue exhibits satisfactory adhesion at a temperature at which it is applied or higher temperatures but has less adhesion at temperatures lower than the above as compared with the conventional pressure sensitive adhesives, so that the pain at the time of peeling from the skin is relieved.
However, the above adhesive and pressure sensitive adhesive are not satisfactory in the capability of sealing a wounded part, the adhesion in wet conditions and the maintenance of adhesion until the wounded part is healed.
That is, when an adhesive plaster provided with the above adhesive or pressure sensitive adhesive is applied to a wounded part, problems arise that a given amount of humidity is present in equilibrium between the adhesive layer and the skin to thereby cause a swell in the skin, and that the adhesive layer only adheres to the skin, so that it is not feasible to protect the wounded part until it is healed.
Therefore, the conventional adhesives and pressure sensitive adhesives (surgical tapes) cannot be stated to have the capability of satisfactorily sealing a wounded part so as to prevent secondary infection in the treatment of the wound. Further, the conventional adhesives and pressure sensitive adhesives have not satisfactory tackiness or adhesion in conditions in which they are in contact with water or in wet conditions attributed to bleeding and body fluid ooze from a wounded part. Still further, at or after the healing of the wounded part, it is preferred that the adhesive and the pressure sensitive adhesive spontaneously peel. In this point as well, it must be stated that the conventional adhesives and pressure sensitive adhesives are not satisfactory. In addition, from the viewpoint of transparency for visual check as well, those of the conventional adhesives and pressure sensitive adhesives are so low that a visual check of the wounded part there through is unfeasible.
The adhesive comprising (2-methacryloyloxy)trimellitate anhydride is described in U.S. Patent No. 4,148,988 issued on Apr. 10, 1979. In this patent, however, there is no disclosure relating to the application thereof to wounded part on soft tissue as proposed in the present invention.
Further, Masaka ("The Effective 4META/MMA-TBB Adhesive Resin on the Conservative Pulp Treatment", Nobuo Masaka, Adhesive Dentistry, 9-16, Vol. 10, No. 1, 1992) teaches that, in the application of an adhesive comprising (2-methacryloyloxy)trimellitate anhydride to teeth, the harm attributed to a direct contact thereof with the dental pulp is slight. However, there is also no disclosure relating to the application thereof to wounded part on soft tissues to join the edges thereof.